Dimethyl phthalate

Repeated dose toxicity: dermal

Administrative data

Endpoint:

chronic toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Acceptable study, which meets basic scientific principles

Data source

Reference

Reference 1

Reference Type:

study report

Title:

Unnamed

Year:

1993

Reference 2

Reference Type:

secondary source

Title:

No information

Author:

ECB-IUCLID

Year:

2000

Bibliographic source:

European Chemicals Bureau, 11-FEB-2000

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 453 (Combined Chronic Toxicity / Carcinogenicity Studies)

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Dimethyl phthalate

EC Number:

205-011-6

EC Name:

Dimethyl phthalate

Cas Number:

131-11-3

Molecular formula:

C10H10O4

IUPAC Name:

1,2-dimethyl benzene-1,2-dicarboxylate

Test material form:

liquid

Specific details on test material used for the study:

Dimethyl phthalate;
colorless liquid, >=99% pure;
Supplied by Chemical Technical Industries, Orlando, Florida,
Lot No.: C122883;
Stability was monitored regularly during the study period, no degradation was observed.

Test animals

Species:

mouse

Strain:

CD-1

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles Rliver Breeding laboratories, Kingston, NY
- Age at study initiation: 7 weeks
- Weight at study initiation:32.6
- Housing: individually
- Diet (e.g. ad libitum): NIN-07 open formula meal ad lib.
- Water (e.g. ad libitum): ad lib.
- Acclimation period: 12 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-25°C
- Humidity (%): 28-74%
- Air changes (per hr): at least 12
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Vehicle:

unchanged (no vehicle)

Details on exposure:

0.1mL of the test substance was applied to the clipped interscapular skin

Duration of treatment / exposure:

1 year (55 weeks)

Frequency of treatment:

5 times/week

Doses / concentrations

Dose / conc.:

2 700 mg/kg bw/day

Remarks:

based on an average weight of 44g, volume administered: 0.1 ml per mouse

No. of animals per sex per dose:

50

Control animals:

yes

Details on study design:

Control animals were treated with acetone, 3 times per week in the first 8 weeks, twice per week thereafter due to skin irritation
Post-exposure period: none

Examinations

Observations and examinations performed and frequency:

CAGE SIDE OBSERVATIONS: Yes
- Time schedule: twice daily
- Cage side observations: Clinical findings, mortality

DETAILED CLINICAL OBSERVATIONS: Yes / No / No data
- Time schedule:

DERMAL IRRITATION (if dermal study): Yes
- Time schedule: weekly

BODY WEIGHT: Yes
- Time schedule for examinations: Weekly for the first 13 weeks, monthly thereafter

Sacrifice and pathology:

GROSS PATHOLOGY: Yes
HISTOPATHOLOGY: Yes
All gross lesions and tissue masses
Adrenal gland, brain, esophagus, gallbladder, heart, kidney, large intestine, liver, lung, mammary gland, mandibular and mesenteric lymph nodes, nose, pancreas, parathyroid gland, pituitary gland, prostate gland, salvary gland, seminal vesicles, skin (site of application and other), small intestine, spleen, sternum, stomach, testis, thymus, thyroid gland, trachea, and urinary bladder

Results and discussion

Results of examinations

Clinical signs:

no effects observed

Dermal irritation:

effects observed, treatment-related

Mortality:

no mortality observed

Body weight and weight changes:

no effects observed

Food consumption and compound intake (if feeding study):

not examined

Food efficiency:

not examined

Water consumption and compound intake (if drinking water study):

not examined

Ophthalmological findings:

not examined

Haematological findings:

not examined

Clinical biochemistry findings:

not examined

Urinalysis findings:

not examined

Behaviour (functional findings):

not examined

Organ weight findings including organ / body weight ratios:

not specified

Gross pathological findings:

no effects observed

Histopathological findings: non-neoplastic:

no effects observed

Histopathological findings: neoplastic:

no effects observed

Effect levels

Dose descriptor:

NOAEL

Effect level:

>= 2 700 mg/kg bw/day

Sex:

male

Basis for effect level:

other: no adverse effects at the highest tested dose

Target system / organ toxicity

Critical effects observed:

no

Any other information on results incl. tables

No effect on survival or growth was reported. 
No microscopic changes in a comprehensive range of tissues were reported 
with the exception of skin irritation at the site of application, which was
observed in treated (11/49) and vehicle control (8/50) animals.